Concurrent PANK2 and OCA2 variants in a patient with retinal dystrophy, hypopigmented irides and neurodegeneration.

PURPOSE: To report a case of concurrent pantothenate kinase-associated neurodegeneration (PKAN) and oculocutaneous albinism (OCA) with dual PANK2 and OCA2 variants in a Chinese patient who presented with early-onset reduced vision, nyctalopia, and neurological symptoms. MATERIALS AND METHODS: Based on the ocular phenotype and provisional diagnosis of rod-cone dystrophy, genetic testing was pursued. Peripheral blood DNA extraction was carried out with the next-generation sequencing technique, which involved a population-specific medical exome virtual panel. Pre- and post-test counseling were carried out by clinical geneticists. RESULT: Homozygous missense variants in PANK2 {NM_153638.3}:c.655 G>A (p.(Gly219Ser)) and OCA2{NM_025160.6}:c.1327 G>A(p.(Val443Ile)) were identified. The molecular diagnoses of pantothenate kinase associated neurodegeneration (OMIM#234200) and albinism, oculocutaneous, type II (OMIM#203200) were supported by clinical findings. CONCLUSION: Two rare autosomal recessive diseases, pantothenate kinase-associated neurodegeneration (PKAN) and oculocutaneous albinism (OCA) were detected in our patient. Ocular and systemic manifestations, as well as neuroimaging findings were compatible with the diseases identified. Genetic analysis is imperative in making an accurate molecular diagnosis in these rare conditions to allow timely counseling, disease prognostication and management.

The Contemporary Role of Photodynamic Therapy in the Treatment of Pachychoroid Diseases.

Recent advances in retinal imaging technology have improved our understanding in the pathogenesis and evolvement of various chorioretinal diseases. Central serous chorioretinopathy and polypoidal choroidal vasculopathy are now recognized to belong to the same spectrum of disorders known as pachychoroid diseases. Pachychoroid diseases have similar pathogenesis pathway and common characteristics of thickened choroid, dilated outer choroidal vessels, and thinning of choriocapillaris. More disease entities have been identified to belong to this disease spectrum. Photodynamic therapy can induce choroidal hypoperfusion, remodeling of abnormal choroidal vessels, and reduction of choroidal congestion. It is known to be an effective treatment for chronic central serous chorioretinopathy and polypoidal choroidal vasculopathy. Many new studies are being performed to investigate its efficacy in other pachychoroid diseases. In this review, we provided an overview of the rationale, efficacy, and treatment strategies of photodynamic therapy in different pachychoroid diseases and discussed its role in the management along with other treatment modalities with most updated clinical evidence.

Fundus Autofluorescence and Optical Coherence Tomography Characteristics in Different Stages of Central Serous Chorioretinopathy.

OBJECTIVE: To describe the morphological changes on fundus autofluorescence (FAF) and spectral-domain optical coherence tomography (SD-OCT) imaging at different chronicity of central serous chorioretinopathy (CSC). METHODS: This cross-sectional study included patients with CSC of different chronicity. Changes in FAF scans and morphological changes on SD-OCT were evaluated and compared at different stages of CSC. RESULTS: Sixty-nine patients were enrolled in the study, with a mean age of 52.1 ± 11.8 years. A distinct hypoautofluorescence (AF) pattern was observed at the leakage point in acute CSC (100%). The leakage site was indistinguishable in 48% of the patients with late-chronic CSC. The majority of acute CSC patients showed hyper-AF in the area of serous retinal detachment (SRD), which persisted in the early-chronic stage of CSC. In late-chronic CSC, many cases of hypo-AF (22.2%) and mixed-pattern AF (14.8%) were observed. SD-OCT revealed evolving features of retinal pigment epithelium (RPE) abnormalities in a time-dependent manner: from peaked PEDs in acute CSC to low-lying PEDs in early-chronic CSC and, eventually, flat, irregular PEDs in late-chronic CSC. The average thickness of the photoreceptor layer (inner and outer segment; IS/OS) was 79 µm in the acute group and 55.2 µm in the chronic group. The photoreceptor layer (IS/OS) height was positively associated with visual acuity (p=0.002). CONCLUSION: Different stages of CSC present different patterns on FAF and SD-OCT imaging. Chronicity of CSC can be estimated using specific features in these images. Photoreceptor layer (IS/OS) height acts as a good and objective predictor of visual outcomes in CSC patients.

Choroidal thickness in thyroid-associated orbitopathy.

IMPORTANCE: To investigate the choroidal thickness (CT) in patients with thyroid-associated orbitopathy (TAO). BACKGROUND: To compare CT of TAO patients and healthy subjects. DESIGN: Prospective cross-sectional study in a public hospital. PARTICIPANTS: One hundred and four eyes of 52 TAO patients and 52 eyes of 26 healthy subjects. METHODS: CT was measured with enhanced-depth imaging optical coherence tomography (EDI-OCT) at the subfoveal, macular and peripapillary regions. Multivariate linear regression was used to evaluate the associations of subfoveal CT with systemic and ocular variables among TAO eyes. MAIN OUTCOME MEASURES: CT of both groups. RESULTS: CT of eyes with TAO was significantly increased at the subfoveal region, 1 and 2 mm from the fovea nasally, temporally and superiorly, and 1 mm inferior to the fovea (all P < .05). No significant difference was found in CT at 2 mm inferior to the fovea (P = .094) and all four quadrants of the peripapillary region (superior, P = .096; nasal, P = .732; inferior, P = .179; temporal, P = .052). Among TAO eyes, thinner subfoveal choroid was associated with worsening exophthalmos (P = .043), poorer visual acuity (P = .017), increasing age (P = .040) and axial length (P < .001). There was no association between CT and clinical activity score (P = .239). CONCLUSIONS AND RELEVANCE: TAO patients showed thicker choroid than controls over the macula, but not the peripapillary regions. Thinner subfoveal choroid was associated with worsening exophthalmos and poorer vision. EDI-OCT can monitor choroidal vascular changes associated with TAO and its complications.

Treatment of cystoid macular edema secondary to retinitis pigmentosa: a systematic review.

There are various treatments for cystoid macular edema (CME) secondary to retinitis pigmentosa; however, the evidence for these treatments has not been previously systematically reviewed. Our review that includes 23 studies shows that oral carbonic anhydrase inhibitors (including acetazolamide and methazolamide) and topical carbonic anhydrase inhibitors (dorzolamide and brinzolamide) are effective first-line treatments. In patients unresponsive to carbonic anhydrase inhibitor treatment, intravitreal steroids (triamcinolone acetonide and sustained-release dexamethasone implants), oral corticosteroid (deflazacort), intravitreal antivascular endothelial growth factor agents (ranibizumab and bevacizumab), grid laser photocoagulation, pars plana vitrectomy, or ketorolac were also effective in improving CME secondary to retinitis pigmentosa. Oral acetazolamide has the strongest clinical basis for treatment and was superior to topical dorzolamide. Rebound of CME was commonly seen in the long term, regardless of the choice of treatment. Oral acetazolamide should be the first-line treatment in CME secondary to retinitis pigmentosa. Topical dorzolamide is an appropriate alternative in patients intolerant to adverse effects of oral acetazolamide. More studies are required to investigate the management of rebound CME.

A Multicenter Study on the Long-term Outcomes of Half-dose Photodynamic Therapy in Chronic Central Serous Chorioretinopathy.

PURPOSE: To investigate long-term efficacy and prognostic factors of half-dose photodynamic therapy (PDT) in chronic central serous chorioretinopathy (CSCR). DESIGN: Retrospective multicenter interventional case series. METHODS: Patients with chronic CSCR undergoing half-dose PDT between 2005 and 2011 were reviewed. Main outcome measures included resolution of serous retinal detachment (SRD) with single PDT, change in best-corrected visual acuities (BCVAs), and recurrence rate of CSCR at 36 months after PDT. Prognostic factors of visual outcome and recurrence of CSCR after PDT were identified with multivariate regression analysis. RESULTS: A total of 136 eyes of 123 patients were followed up for 57.7 ± 16.2 months. At 36 months after PDT, 132 eyes (97.1%) achieved complete resolution of SRD with single PDT and 4 eyes (2.9%) had CSCR recurrence. The mean logMAR BCVA improved from 0.36 ± 0.29 (Snellen equivalent 20/46; range: 0.1-1.2) at baseline to 0.15 ± 0.23 at 36 months (Snellen equivalent 20/28; range: 0.1-1.5; P < .001) and 0.16 ± 0.24 (Snellen equivalent: 20/29; range: 0.1-1.5; P < .001) at final follow-up. Forty-four eyes (32.4%) had ≥3 lines of BCVA gain while 5 eyes (3.7%) had ≥3 lines of BCVA loss at 36 months after PDT. Nine eyes (6.6%) developed CSCR recurrence at final follow-up. Baseline BCVA was significantly associated with the BCVA (P = .009) and the improvement in BCVA (P < .001) at final follow-up. History of bilateral CSCR was significantly associated with CSCR recurrence at final follow-up (P = .036; odds ratio = 15.84, 95% confidence interval = 1.20-208.32). Eight eyes (5.9%) had complications related to PDT. CONCLUSIONS: Chronic CSCR patients treated with half-dose PDT can achieve long-term stable visual acuity and resolution of SRD. Patients with chronic CSCR are recommended to undergo half-dose PDT before they have significant visual deterioration. Patients with bilateral CSCR are more likely to develop CSCR recurrence after half-dose PDT.

Combined pars plana vitrectomy-scleral buckle versus pars plana vitrectomy for proliferative vitreoretinopathy.

The purpose of the study is to evaluate the surgical outcomes of combined pars plana vitrectomy-scleral buckle (PPV-SB) versus pars plana vitrectomy (PPV) for rhegmatogenous retinal detachment complicated with proliferative vitreoretinopathy (PVR). One thousand one hundred and seventy four patients with rhegmatogenous retinal detachment surgery between January 2002 and December 2013 were retrospectively reviewed. Patients with grade C PVR treated with either combined PPV-SB or PPV alone were included in the study. Study outcomes included single surgery anatomic success rate and postoperative visual outcome at 12 months postoperatively. Seventy-seven patients with grade C PVR were identified for analysis. At the end of 12-month follow-up, 80.5 % eyes (33/41) in the PPV-SB group and 58.3 % eyes (21/36) in the PPV group achieved single surgery anatomical success. In a multiple logistic regression model, none of the baseline variables (age, gender, macula status, grade of PVR, extent of detachment, presence of vitreous hemorrhage, lens status, status of high myopia) nor types of retinal detachment surgery (use of scleral buckle, barrier endolaser, 360 degree endolaser, cryopexy, retinectomy, tamponade agent, phacoemulsification) had significant effect on single surgery anatomical success. The post-treatment mean logMAR visual acuity of the PPV-SB group was 1.58 ± 0.58 and the PPV group was 1.57 ± 0.61. There was no significant difference in the postoperative visual acuity between the two groups (P = 0.849). For patients with grade C PVR, PPV-SB did not demonstrate a superiority over PPV alone in achieving single surgery anatomical success.

Ethnic differences in the association of SERPING1 with age-related macular degeneration and polypoidal choroidal vasculopathy.

Neovascular age-related macular degeneration (AMD) and polypoidal choroidal vasculopathy (PCV) are leading causes of irreversible blindness in developed countries. In this study, we investigated the association of single nucleotide polymorphisms (SNPs) in the serpin peptidase inhibitor, clade G, member 1 (SERPING1) gene with neovascular AMD and PCV. Two haplotype-tagging SNPs, rs1005510 and rs11603020, of SERPING1 were genotyped in 708 unrelated Chinese individuals: 200 neovascular AMD, 233 PCV and 275 controls. A meta-analysis was also performed for all reported associations of SERPING1 SNPs with AMD and PCV. None of the tagging SNPs had a significant association with neovascular AMD or PCV (P > 0.05) in our study cohort. The meta-analyses showed that the most-studied SNP rs2511989 was not significantly associated with all forms of AMD, neovascular AMD, or PCV in East Asians (P = 0.98, 0.93 and 0.30, respectively) but was associated with AMD in Caucasians (P = 0.04 for all AMD and 0.004 for neovascular AMD). Therefore, the results of our study and meta-analysis suggest that SERPING1 is not a major genetic component of AMD or PCV in East Asians but is a genetic risk factor for AMD in Caucasians, providing evidence for an ethnic diversity in the genetic etiology of AMD.

Clinical outcomes of cataract surgery in very elderly adults.

OBJECTIVES: To investigate the clinical outcomes of cataract surgery elderly adults. DESIGN: Retrospective cohort study. SETTING: Two clustered hospitals. PARTICIPANTS: Two hundred seven individuals aged 90 and older who underwent cataract surgery for primary senile cataracts. MEASUREMENTS: Best-corrected preoperative and postoperative Snellen visual acuity, type of cataract, surgical techniques, preoperative systemic or ocular comorbidities, and intraoperative and postoperative complications were assessed. Improvement of visual acuity was defined as a decrease in logMAR acuity of 0.1. Factors associated with visual outcome within 6 months after surgery were identified using logistic regression modeling. The duration of postoperative survival was calculated. RESULTS: In the 207 participants (mean age 92.0 ± 2.1), 79.7% achieved visual improvement after cataract surgery. Forty-eight percent (mean age 97.4 ± 2.8) were alive on December 31, 2012. The most common systemic comorbidities were hypertension (66.2%), diabetes mellitus (25.1%), and myocardial infarction (19.8%). Age-related macular degeneration (AMRD) (15.9%), glaucoma (10.6%), and myopic degeneration (5.3%) were the three most common ocular comorbidities. Uncomplicated cataract surgery was performed in 87.0% cases. The most common complications were vitreous loss (8.2%), posterior capsular rupture (7.2%), and zonular rupture (4.8%). Participants with AMRD (P = .001, odds ratio (OR) = 4.77, 95% confidence interval (CI) = 1.86-12.26) and vitreous loss (P = .001, OR = 12.86, 95% CI = 2.71-61.10) were less likely to achieve postoperative visual improvement. CONCLUSION: Despite a high prevalence of systemic and ocular comorbidities in very elderly adults, good clinical outcomes of cataract surgery were attainable. ARMD and vitreous loss were associated with a lower chance of postoperative visual improvement.

Randomized trial on silicone intubation in endoscopic mechanical dacryocystorhinostomy (SEND) for primary nasolacrimal duct obstruction.

PURPOSE: To study the effect of bicanalicular silicone intubation on endonasal endoscopic mechanical dacryocystorhinostomy (EEM-DCR) for primary acquired nasolacrimal duct obstruction (PANDO). DESIGN: Randomized clinical trial. PARTICIPANTS: A total of 120 consecutive adults (103 females) with a presenting age of 64 ± 13.7 years (range, 39-92 years) underwent EEM-DCR for PANDO from November 2005 to May 2009 in a lacrimal referral center. METHODS: The EEM-DCR was performed by 2 lacrimal surgeons using standard techniques. Patients were randomly assigned to receive or not receive bicanalicular silicone intubation for 8 weeks. No antimetabolite was used. All patients received a course of oral antibiotics during nonabsorbable nasal packing for flaps tamponade, which was removed at the first postoperative visit. Patients were assessed at 1, 3, 6, 12, 26, and 52 weeks after the operation. MAIN OUTCOME MEASURES: Surgical success was defined by symptomatic relief of epiphora, reestablishment of nasolacrimal drainage confirmed by irrigation by 1 masked observer, and positive functional endoscopic dye test by the operative surgeon at 12 months postoperatively. Intraoperative and postoperative complications were recorded. RESULTS: A total of 118 of the 120 randomized cases completed 12 months of follow-up. Two patients died of unrelated medical illnesses during follow-up. At 12 months postoperatively, there was no statistical difference in the success rate between patients with (96.3%) and without (95.3%) intubation (P=0.79). The odds ratio of failure without silicone intubation was 1.28 (95% confidence interval, 0.21-7.95). There was no difference in the incidence (P=0.97) or the time to develop (P=0.12) granulation tissue between the 2 groups. No significant difference was found between successful and failed cases in terms of age (P=0.21), sex (P=0.37), laterality (P=0.46), mode of anesthesia (P=0.14), surgeon (P=0.26), use of stent (P=0.79), or presence of granulation tissue postoperatively (P=0.39). CONCLUSIONS: The current study design provided 90% statistical power to detect more than 21% difference in surgical outcome, and no such difference was found whether intubation was used or not used in EEM-DCR for PANDO at the 12-month follow-up. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Review of Intermediate Uveitis.

The purpose of this article is to highlight evidence about the medical and surgical management of intermediate uveitis (IU). Updated understandings of the immunopathology of IU were reviewed in this retrospective literature review. Literature selection for this review was based on the PubMed database (National Library of Medicine) and OVID database (Wolters Kluwer). Articles deemed relevant were selected and highlighted. Intermediate uveitis is most often a benign form of uveitis. Since intermediate uveitis has been described in association with different systemic disorders, the initial diagnostic evaluation should serve to exclude masquerade syndromes and infectious diseases in which immunosuppression may be ineffective or contraindicated. Although the pathogenesis of intermediate uveitis is not fully understood, identification of proinflammatory molecules involved in the IU has contributed to the development and implementation of new therapies. Studies about the use of various immunosuppressants, biological agents and surgical treatment on IU have provided more evidence for managing IU. Nevertheless, corticosteroids remain the mainstay of treatment. The treatment options of intermediate uveitis are evolving, with the development of various immunosuppressants and biological agents. The management of intermediate uveitis should be tailored individually, based on specific causes of the disease and associated complications.